Azaphenothiazine is a valuable precursor for pharmaceutically active substances such as pipacetate (INN) Selvigon.RTM., Isothipendyl (INN) (Andantol.RTM.) and prothipendyl (INN) (Dominal.RTM.). The synthesis of the compound is described in German Patent DE-PS 964050 as well as in J. Org. Chem. 25, pp. 1156-1157 (1959). The synthesis starts with 2-phenylaminopyridine and elementary sulfur and proceeds by means of cyclization in the melt, using iodine catalysis. The process has several disadvantages: a mole of H.sub.2 S is formed as a by-product; a high reaction temperatures of 230.degree. C.-250.degree. C. is necessary, in contrast to benzothiazines (phenothiazines); the workup procedure is expensive. The sulfonation reagents SCl.sub.2 and S.sub.2 Cl.sub.2 used, under rather mild conditions in the process described in the German patent leads to unsatisfactory yields when the process is repeated.
In addition to this one-stage method starting from 2-phenylaminopyridine, multi-stage methods are known from the work of H. L. Yale and E. Sowinski, J. Org. Chem., p. 1651 (1958) and French Patent Application FR No. 1,170,119 which methods start either from 2-chloro-3-aminopyridine or 2-chloro-3-nitropyridine and 2-aminothiophenol (2-mercaptoaniline) (the so-called Smiles rearrangement cf. N. L. Smiles, J., Org. Chem. 15, 1125 (1950) and R. R. Gystra (Ed.) Phenothiazines and 1,4-benzothiazines--Chemical and Biomedical Aspects, Elsevier, Amsterdam 1988), (U.S. Pat. No. 2,943,086) or 2-chloro-3-mercaptopyridine and 2-chloro-nitrobenzene. Both methods were incapable of being scaled up to an industrial process for economic reasons.
In all the methods cited, the target compound is purified as a base using vacuum distillation, and then by salt formation.
This purification method stresses the product thermally and results in residues which must be disposed of as special waste, because they can not be re-utilized. Purification via salt formation requires a further additional method step and raises the expense.
There is, therefore, a need for a method which avoids the described disadvantages of the state of the art and which, moreover, meets the requirements placed on the environmental compatibility of production methods, which requirements have increased since those methods were developed, by avoiding byproducts and high reaction temperatures. In addition, it is advantageous to save a few method steps.